Suicidal ideation during treatment of depression with escitalopram and nortriptyline in Genome-Based Therapeutic Drugs for Depression (GENDEP): a clinical trial

BMC Medicine

Katherine J Aitchison⁵  Peter McGuffin⁵  Anne E Farmer⁵  Bhanu Gupta⁵  Desmond Campbell⁵  Joanna Gray⁵  Cerisse Gunasinghe⁵  Amanda Elkin⁵  Caterina Giovannini⁷  Astrid Zobel⁸  Jana Strohmaier⁶  Lisbeth Jorgensen³  Aleksandra Szczepankiewicz⁹  Anna Placentino⁷  Daniel Souery^1,10  Wolfgang Maier⁸  Joanna Hauser⁹  Neven Henigsberg¹  Ole Mors²  Marcella Rietschel⁶  Andrej Marusic⁴  Rudolf Uher⁵  Nader Perroud⁵ 

[1] Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia;Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark;Mood Disorders Research Unit, Aarhus University Hospital, Risskov, Denmark;Institute of Public Health, Ljubljana, Slovenia;MRC SGDP Centre, Institute of Psychiatry at King's College London, UK;Central Institute of Mental Health, Division of Genetic Epidemiology in Psychiatry, Mannheim, Germany;Biological Psychiatry Unit and Dual Diagnosis Ward IRCCS, Centro San Giovanni di Dio, Brescia, Italy;Department of Psychiatry, University of Bonn, Bonn, Germany;Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland;Université Libre de Bruxelles, Erasme Academic Hospital, Department of Psychiatry, Brussels, Belgium

Others  :  1128889
DOI  :  10.1186/1741-7015-7-60

 received in 2009-09-14, accepted in 2009-10-15,  发布年份 2009

【 摘 要 】

Background

Suicidal thoughts and behaviours during antidepressant treatment, especially during the first weeks of treatment, have prompted warnings by regulatory bodies. The aim of the present study is to investigate the course and predictors of emergence and worsening of suicidal ideation during tricyclic antidepressant and serotonin reuptake inhibitor treatment.

Methods

In a multicentre part-randomised open-label study, 811 adult patients with moderate to severe unipolar depression were allocated to flexible dosage of escitalopram or nortriptyline for 12 weeks. The suicidality items of three standard measures were integrated in a suicidal ideation score. Increases in this score were classified as treatment emergent suicidal ideation (TESI) or treatment worsening suicidal ideation (TWOSI) according to the absence or presence of suicidal ideation at baseline.

Results

Suicidal ideation decreased during antidepressant treatment. Rates of TESI and TWOSI peaked in the fifth week. Severity of depression predicted TESI and TWOSI. In men, nortriptyline was associated with a 9.8-fold and 2.4-fold increase in TESI and TWOSI compared to escitalopram, respectively. Retirement and history of suicide attempts predicted TWOSI.

Conclusion

Increases in suicidal ideation were associated with depression severity and decreased during antidepressant treatment. In men, treatment with escitalopram is associated with lower risk of suicidal ideation compared to nortriptyline. Clinicians should remain alert to suicidal ideation beyond the initial weeks of antidepressant treatment.

Trial registration

EudraCT (No.2004-001723-38) and ISRCTN (No. 03693000).

【 授权许可】

   
2009 Perroud et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]World Health Organization Suicide prevention guidelines [http:/ / www.who.int/ mental_health/ prevention/ suicide/ suicideprevent/ en/ print.html] webcite
• [2]Henriksson S, Boethius G, Isacsson G: Suicides are seldom prescribed antidepressants: findings from a prospective prescription database in Jamtland county, Sweden, 1985-95. Acta Psychiatr Scand 2001, 103:301-306.
• [3]Lonnqvist JK, Henriksson MM, Isometsa ET, Marttunen MJ, Heikkinen ME, Aro HM, Kuoppasalmi KI: Mental disorders and suicide prevention. Psychiatry Clin Neurosci 1995, 49(Suppl 1):S111-116.
• [4]Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Hebert P, Hutton B: Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ 2005, 330:396.
• [5]Gunnell D, Saperia J, Ashby D: Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review. BMJ 2005, 330:385.
• [6]Suicide prevention in Europe. The WHO European monitoring survey on national suicide prevention programmes and strategies [http://www.euro.who.int/document/E77922.pdf] webcite
• [7]Clinical review: relationship between antidepressant drugs and suicidality in adults [http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf] webcite
• [8]Valuck RJ, Libby AM, Orton HD, Morrato EH, Allen R, Baldessarini RJ: Spillover effects on treatment of adult depression in primary care after FDA advisory on risk of pediatric suicidality with SSRIs. Am J Psychiatry 2007, 164:1198-1205.
• [9]Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, McMahon FJ: Genetic markers of suicidal ideation emerging during citalopram treatment of major depression. Am J Psychiatry 2007, 164:1530-1538.
• [10]Nelson JC, Delucchi K, Schneider L: Suicidal thinking and behavior during treatment with sertraline in late-life depression. Am J Geriatr Psychiatry 2007, 15:573-580.
• [11]Perlis RH, Beasley CM Jr, Wines JD Jr, Tamura RN, Cusin C, Shear D, Amsterdam J, Quitkin F, Strong RE, Rosenbaum JF, et al.: Treatment-associated suicidal ideation and adverse effects in an open, multicenter trial of fluoxetine for major depressive episodes. Psychother Psychosom 2007, 76:40-46.
• [12]Perlis RH, Purcell S, Fava M, Fagerness J, Rush AJ, Trivedi MH, Smoller JW: Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study. Arch Gen Psychiatry 2007, 64:689-697.
• [13]Szanto K, Mulsant BH, Houck PR, Dew MA, Dombrovski A, Pollock BG, Reynolds CF 3rd: Emergence, persistence, and resolution of suicidal ideation during treatment of depression in old age. J AffectDisord 2007, 98:153-161.
• [14]Jick H, Kaye JA, Jick SS: Antidepressants and the risk of suicidal behaviors. JAMA 2004, 292:338-343.
• [15]Zisook S, Trivedi MH, Warden D, Lebowitz B, Thase ME, Stewart JW, Moutier C, Fava M, Wisniewski SR, Luther J, et al.: Clinical correlates of the worsening or emergence of suicidal ideation during SSRI treatment of depression: An examination of citalopram in the STARD study. J Affect Disord 2009, 117:63-73.
• [16]Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, Gelenberg AJ, Davis SM, Harrison WM, Keller MB: Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry 2000, 157:1445-1452.
• [17]Martinez C, Rietbrock S, Wise L, Ashby D, Chick J, Moseley J, Evans S, Gunnell D: Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study. BMJ 2005, 330:389.
• [18]Donovan S, Clayton A, Beeharry M, Jones S, Kirk C, Waters K, Gardner D, Faulding J, Madeley R: Deliberate self-harm and antidepressant drugs. Investigation of a possible link. Br J Psychiatry 2000, 177:551-556.
• [19]Embretson S, Reise S: Item response theory for psychologists. Mahwah, NJ, USA: Erlbaum; 2000.
• [20]Uher R, Farmer A, Maier W, Rietschel M, Hauser J, Marusic A, Mors O, Elkin A, Williamson RJ, Schmael C, et al.: Measuring depression: comparison and integration of three scales in the GENDEP study. Psychol Med 2008, 38:289-300.
• [21]Uher R, Maier W, Hauser J, Marusic A, Schmael C, Mors O, Henigsberg N, Souery D, Placentino A, Rietschel M, et al.: Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression. Br J Psychiatry 2009, 194:252-259.
• [22]Grayson D, Bridges K, Cook D, Goldberg D: The validity of diagnostic systems for common mental disorders: a comparison between the ID-CATEGO and the DSM-III systems. Psychol Med 1990, 20:209-218.
• [23]Bech P, Gram LF, Dein E, Jacobsen O, Vitger J, Bolwig TG: Quantitative rating of depressive states. Acta Psychiatr Scand 1975, 51:161-170.
• [24]Ruhe HG, Dekker JJ, Peen J, Holman R, de Jonghe F: Clinical use of the Hamilton Depression Rating Scale: is increased efficiency possible? A post hoc comparison of Hamilton Depression Rating Scale, Maier and Bech subscales, Clinical Global Impression, and Symptom Checklist-90 scores. Compr Psychiatry 2005, 46:417-427.
• [25]Rabe-Hesketh S, Skrondal A: Multilevel and longitudinal modeling using Stata. College Station, TX, USA: Stata Press; 2005.
• [26]QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies [http://hydra.usc.edu/gxe] webcite
• [27]Juurlink DN, Mamdani MM, Kopp A, Redelmeier DA: The risk of suicide with selective serotonin reuptake inhibitors in the elderly. Am J Psychiatry 2006, 163:813-821.
• [28]Hammad TA, Laughren TP, Racoosin JA: Suicide rates in short-term randomized controlled trials of newer antidepressants. J Clin Psychopharmacol 2006, 26:203-207.
• [29]US Federal Drug Administration: Important Prescribing Information [http://www.fda.gov/medWatch/SAFETY/2006/paroxetineDHCPMay06.pdf] webcite
• [30]Aursnes I, Tvete IF, Gaasemyr J, Natvig B: Suicide attempts in clinical trials with paroxetine randomised against placebo. BMC Med 2005, 3:14. BioMed Central Full Text
• [31]Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Tanskanen A, Haukka J: Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort. Arch Gen Psychiatry 2006, 63:1358-1367.
• [32]Sharma A, Busnello JV, Ribeiro L, Thakur S, Whelan F, Elashoff RM, Wong ML, Licinio J: Suicidality scores during double-blind fluoxetine and desipramine treatment in Mexican Americans. J Clin Psychopharmacol 2007, 27:99-101.
• [33]Hall WD: How have the SSRI antidepressants affected suicide risk? Lancet 2006, 367:1959-1962.
• [34]Ohberg A, Vuori E, Klaukka T, Lonnqvist J: Antidepressants and suicide mortality. J Affect Disord 1998, 50:225-233.
• [35]Grunebaum MF, Ellis SP, Li S, Oquendo MA, Mann JJ: Antidepressants and suicide risk in the United States, 1985-1999. J Clin Psychiatry 2004, 65:1456-1462.
• [36]Carlsten A, Waern M, Ekedahl A, Ranstam J: Antidepressant medication and suicide in Sweden. Pharmacoepidemiol Drug Saf 2001, 10:525-530.
• [37]Cipriani A, Barbui C, Geddes JR: Suicide, depression, and antidepressants. BMJ 2005, 330:373-374.
• [38]Bondy B, Buettner A, Zill P: Genetics of suicide. Mol Psychiatry 2006, 11:336-351.
• [39]Benazzi F: Mixed depression, suicidality, and antidepressants. J Clin Psychiatry 2006, 67:1650-1651.
• [40]Zisook S, Lesser I, Stewart JW, Wisniewski SR, Balasubramani GK, Fava M, Gilmer WS, Dresselhaus TR, Thase ME, Nierenberg AA, et al.: Effect of age at onset on the course of major depressive disorder. Am J Psychiatry 2007, 164:1539-1546.
• [41]Beasley CM Jr, Ball SG, Nilsson ME, Polzer J, Tauscher-Wisniewski S, Plewes J, Acharya N: Fluoxetine and adult suicidality revisited: an updated meta-analysis using expanded data sources from placebo-controlled trials. J Clin Psychopharmacol 2007, 27:682-686.
• [42]Balon R: Selective serotonin reuptake inhibitors and suicide: is the evidence, as with beauty, in the eye of the beholder? Psychother Psychosom 2003, 72:293-299.
• [43]Hirschfeld RM, Russell JM: Assessment and treatment of suicidal patients. N Engl J Med 1997, 337:910-915.
• [44]Agerbo E, Gunnell D, Bonde JP, Mortensen PB, Nordentoft M: Suicide and occupation: the impact of socio-economic, demographic and psychiatric differences. Psychol Med 2007, 37:1131-1140.
• [45]Brent DA, Mann JJ: Family genetic studies, suicide, and suicidal behavior. Am J Med Genet C Semin Med Genet 2005, 133C:13-24.